Carotid intima-media thickness (CIMT) and apolipoproteins have been found as a risk factor for ischemic stroke
The objective was to study the carotid intima-media thickness, apolipoproteins, and their relation in patients of ischemic stroke in central rural India.
Settings and Design:
A cross-sectional study was performed in a rural hospital in central India.
Materials and Methods:
In all patients of ischemic stroke proven by computerized tomography (CT), CIMT, apolipoprotein A-I (ApoA-I), and apolipoprotein B(ApoB) were measured.
Statistical Analysis Used:
We used Student’s t-test to compare means, a chi-square test to compare proportions, and a Mann-Whitney test to compare medians. A P value <0.05 was considered significant.
The mean age of our study population (N=106) was 61 years. The mean CIMT was 0.83 mm ranging from a minimum of 0.45 mm to a maximum of 1.096 mm. Mean CIMT was significantly higher than expected 0.67 values, which was calculated according to the age of the study population. The association of decreased ApoA-I < 100 mg/dl and increased ApoB > 90 mg/dl with CIMT > 0.7 mm was statistically significant with P<0.001.
The CIMT in computerized tomography-proven ischemic stroke was significantly higher than expected for the age of the study population. The relation of decreased ApoA-I and increased ApoB with CIMT > 0.7 mm was also statistically significant.Keywords: Atherosclerosis, apolipoproteins, carotid arteries, Carotid intima-media thickness, stroke
Stroke is one of the leading causes of morbidity and mortality in the world today. There has been a constant effort on the part of medical researchers to analyze this problem and search for factors that aid in its prevention. Carotid intima-media thickness (CIMT) measurement has emerged as one of the noninvasive methods of choice for determining preclinical (asymptomatic) atherosclerotic changes.[2,3] CIMT is a marker of subclinical atherosclerosis, a strong predictor of subsequent cardiovascular and cerebrovascular morbidity.[4,5] Measurement of CIMT, the anatomic extent of atherosclerosis and its progression helps in identifying high risk subjects, who are candidates of primary prevention.
The development of sonography technology has allowed the noninvasive evaluation of atherosclerosis in the carotid arteries. The initial manifestation of carotid atherosclerosis is characterized by a subtle increase in vascular IMT, the progression of which leads to plaque formation and vascular narrowing. Reflecting systemic atherosclerosis, increased CIMT is associated with a higher risk for stroke.
Early detection of atherosclerosis is desirable for the primary and or secondary prevention of atherosclerotic events like stroke and myocardial infarction. Similarly, the risk of stroke increases with increasing CMIT.
Atherosclerosis is the leading cause of occlusive arterial disease in patients over 40 years old; the highest incidence occurs in the sixth and seventh decades of life. The strongest predictors of CIMT, after adjusting for age and sex, were total cholesterol and smoking status besides ethnicity (African American versus white).[2,6] Apolipoprotein B (ApoB) and apolipoprotein A-I (ApoA-I) are identified as risk factors for cardiovascular and possibly cerebrovascular diseases. It has been documented in certain studies that ApoA-I is inversely related to the CIMT; this is specifically significant in cases of documented cerebrovascular diseases. An increase in ApoB and a decrease in ApoA-I indicate an increased risk for atherosclerotic complications.
Apolipoproteins are good predictors of subsequent cerebrovascular events, and improve on predictions by conventional risk factors alone. Their use is simple and accurate and could be included in routine screening of cerebrovascular status.
Thus, the present study was carried out to measure CIMT and ApoB/ApoA-I ratio and demonstrate the correlation between them in patients of more than 18 years of age with ischemic stroke proven by computerized tomography (CT) in a resource-constrained setting in central rural India.
Materials and Methods
The study was approved by the ethics committee of Mahatma Gandhi Institute of Medical Sciences (IRB00003623). We obtained a written informed consent from all study participants before enrolling them in the study.
We did this study in the department of Medicine and Radiology at Kasturba Hospital and Mahatma Gandhi Institute of Medical Sciences (MGIMS), Sevagram. Kasturba Hospital is a 720-bed rural teaching hospital of central India affiliated to MGIMS. Every year this hospital provides care to about 400,000 outpatients and 40,000 inpatients. In an inpatient setting, physicians typically order CT scan of brain estimation in patients clinically judged to have stroke, in all patients who come for treatment. We enrolled patients from inpatient settings in this study.
Since 1 May 2006 to 30 December 2007, we enrolled all consecutive inpatients with admission diagnosis of ischemic stroke proven by CT of more than 18 years of age in a cross-sectional observational study.
The diagnosis of ischemic stroke was based on the clinical profile and confirmed by CT as defined by ASA/AHA. Ischemic stroke was defined as an abrupt onset, nonconvulsive, focal neurological deficit probably vascular in origin lasting for more than 24 hours on the clinical profile and in neuroimaging studies demonstrating a recent, appropriately located ischemic lesion on CT scan. Criteria for exclusion were recurrent stroke, normal CT scan of brain, CT scan showed hemorrhage, CT scan not feasible, and patients not consenting to the study.
Baseline characteristics and clinical data were recorded for all patients. All patients received the standard line of management for stroke in accordance with ASA/AHA guidelines.
Measurement of carotid intima-media thickness
The measurements of CIMT were obtained by using a Logic Pro 2000 MDMR3 ultrasound system, equipped with a 7.5 MHz real-time, linear-array transducer B-mode scanner to examine the patient’s ultrasound images of the common carotid artery, carotid bifurcation, and the internal carotid artery after admission in all enrolled patients’ CT scan-proven stroke carotid arteries. A single experienced operator carried out all ultrasonographic investigations.
Patients were asked to lie supine with the neck extended in a slightly lateral rotation. Then carotid artery and the lumen of the carotid artery beneath the surface of the neck were scanned. CIMT was defined as the distance between the leading edge of the first bright line (lumen intima interface) and the leading edge of the second bright line (media-adventitia interface) of the posterior (far) wall of the vessel and for the anterior (near) wall, between the trailing edge of the first bright line and the trailing edge of the second bright line. Three sites were selected in each carotid artery. CIMT was measured on the frozen frame of a suitable longitudinal image with the image magnified to achieve a higher resolution of detail. The first reading was taken 1 cm proximal to the carotid bulb while the second at a maximum diameter of the carotid bulb. The third reading was taken 1 cm distal to the carotid bulb along the internal carotid artery. For all three sites, both near wall and far wall measurements were taken. The average of each artery was computed taking into all six readings as (A+B+C+D+E+F)/6, where A= far wall of CCA, B= near wall of CCA, C= far wall of carotid bulb, D= near wall of carotid bulb, E= far wall of internal carotid artery (ICA), F= near wall of ICA.
The CIMT expected for age of the patient was calculated using the formula CIMT = (0.009×Age) + 0.116. The mean expected CIMT was 0.67 mm calculated according to the age of the study patients. Therefore CIMT > 0.7 mm is considered as the abnormal value.
Measurement of biochemical markers
Sera from all enrolled patients were collected for estimation of ApoB, ApoA-I on admission. The collected sera were stored at –20°c till they were tested by serologist who was unaware of the clinical data of the patients. ApoB, ApoA-I estimation was done on a fully automated BN-nephelometry system. Levels of ApoA-I were said to be low if they were < 100 mg/dl and of Apo B were said to be high if they were more than 90 mg/dl. The ApoB/ApoA-I ratio was considered to be high if it was > or equal to 0.8.
Venous blood samples drawn after a 12-hour overnight fast were immediately refrigerated and transported within 6 hours to central laboratory of hospital for total cholesterol, high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides measurement by standard enzymatic tests. Levels were considered abnormal if total cholesterol > 200 mg/dl, LDL-C >130 mg/dl ,triglycerides >150mg/dl, and HDL-C < 40 mg/dl respectively. Random glucose and serum creatinine were also obtained on day 1 in all enrolled participants. During the hospital stay, patients were monitored daily for any complications.
We screened 207 consecutive patients of stroke for our study, between 1 May 2006 and 30 December and enrolled 106 patients of stroke who fulfilled our study inclusion criteria.
We entered the data electronically by Microsoft Excel and analyzed by STATA software (Version 10, Stata Corporation, Texas, USA). We analyzed normally distributed continuous variables by Student’s t-test, proportions by a chi-square test, and continuous variables with skewed distribution by a Mann-Whitney test. The association of CIMT and apolipoproteins was calculated by the correlation coefficient.